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This energy is a symmetrised version of the minimum separation component of the loss used to design peptide binders in: ‘Li, Q., Vlachos, E.N. & Bryant, P. Design of linear and cyclic peptide binders from protein sequence information. Commun Chem 8, 211 (2025)’ DOI https://doi.org/10.1038/s42004-025-01601-3 Note in this reference the explanation of Eq.1 is misleading. Here, the average of the minimum distance is over all the the residues in the first group.

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Definition

The FlexEvoBind energy computes the average minimum inter-atomic distance between two residue groups, adapted from the binding loss in Li et al. 2025. For each residue in group 1, the minimum distance to any atom in group 2 is found, and these minimum distances are averaged. When symmetrized=True (the default), the same calculation is performed from group 2 to group 1, and a weighted average of both directions is taken. When plddt_weighted=True, each direction is divided by its group’s average pLDDT, producing a formulation closer to the EvoBind loss.

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Parameters

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oracle
FoldingOracle
required
The oracle to use for the energy term.
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residues
tuple[list[Residue], list[Residue]]
required
A tuple containing two lists of residues, those to include in the first [0] and second [1] group.
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plddt_weighted
bool
default:"False"
A bool indicating whether the result need to be weighted by the plddt of the residues considered. If True, this definition is closer to the EvoBind energy in the reference below
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symmetrized
bool
default:"True"
A bool indicating whether or not the calculation of the minimum distances need to be symmetrized between residues in residued[0] and those in residues[1]. Otherwise the minimum distances are those between any atom in residues from residues[0] and those in residues in residues[1], but not vice versa.
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inheritable
bool
default:"True"
If a new residue is added next to a residue included in this energy term, this dictates whether that new residue could then be added to this energy term.
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weight
float
default:"1.0"
The weight of the energy term.
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name
str | None
default:"None"
Optional name to append to the energy term name.

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Methods

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compute

Parameters
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oracles_result
OraclesResultDict
required

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Example

import bagel as bg

# Create the folding oracle
esmfold = bg.oracles.ESMFold()

# Define two groups of residues (e.g. hotspot and binder)
hotspot_residues = [residues_target[i] for i in range(10, 20)]
binder_residues = residues_binder

# Minimize average minimum distance between two residue groups
flex_evo_bind = bg.energies.FlexEvoBindEnergy(
    oracle=esmfold,
    residues=[hotspot_residues, binder_residues],
    symmetrized=True,
    weight=1.0,
)

# Add to a state
state = bg.State(
    chains=[binder_chain, target_chain],
    energy_terms=[flex_evo_bind],
    name="my_state",
)